Chloromethyl Methyl Ether → 1-Bromo-4-fluoro-2-(methoxymethoxy)benzene

HRID 423178Notes

Reaction equation

HRID 423178 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[OH:9].C(N(C(C)C)CC)(C)C.[CH3:19][O:20][CH2:21]Cl>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[O:9][CH2:19][O:20][CH3:21]

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 27246002-Bromo-5-fluorophenol

Product 1

HCID 108236251-Bromo-4-fluoro-2-(methoxymethoxy)benzeneYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-Bromo-5-fluorophenol (30 g, 0.16 mol) is dissolved in dichloromethane (170 mL) and cooled to 0° C. To this solution is added diisopropylethylamine (36 mL, 0.20 mol) via syringe followed by chloromethyl methyl ether (16 mL, 0.20 mol) via an addition funnel. The solution is stirred and warmed to room temperature. After 2 h, the mixture is washed with saturated aqueous NH4Cl, water, and brine. The organic portion is dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (Biotage® Si65M, 20% AcOEt/hexane) to yield 26.1 g (71%) of the title compound as a clear colorless oil. 1H NMR 400 MHz (CDCl3) δ 7.46-7.53 (m, 1H), 6.92-6.99 (m, 1H), 6.63-6.70 (m, 1H), 5.26 (s, 2H), 3.55 (s, 3H).

Workup

  1. temperaturewarmed to room temperature
  2. washthe mixture is washed with saturated aqueous NH4Cl, water, and brine
  3. dry with materialThe organic portion is dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is purified by flash chromatography (Biotage® Si65M, 20% AcOEt/hexane)

Sources & evidence

ORD record
ord-6afa7cb1fbf24f8ba2dd881ed75ea49a
Source dataset
uspto-grants-2012_01
Patent number
US08101761B2

Reaction notes

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